Ultra-low-dose CT vs. chest X-ray in non-traumatic emergency department patients – a prospective randomised crossover cohort trial

Summary Background Ultra-low-dose CT (ULDCT) examinations of the chest at only twice the radiation dose of a chest X-ray (CXR) now offer a valuable imaging alternative to CXR. This trial prospectively compares ULDCT and CXR for the detection rate of diagnoses and their clinical relevance in a low-prevalence cohort of non-traumatic emergency department patients. Methods In this prospective crossover cohort trial, 294 non-traumatic emergency department patients with a clinically indicated CXR were included between May 2nd and November 26th of 2019 (www.clinicaltrials.gov: NCT03922516). All participants received both CXR and ULDCT, and were randomized into two arms with inverse reporting order. The detection rate of CXR was calculated from ‘arm CXR’ (n = 147; CXR first), and of ULDCT from ‘arm ULDCT’ (n = 147; ULDCT first). Additional information reported by the second exam in each arm was documented. From all available clinical and imaging data, expert radiologists and emergency physicians built a compound reference standard, including radiologically undetectable diagnoses, and assigned each finding to one of five clinical relevance categories for the respective patient. Findings Detection rates for main diagnoses by CXR and ULDCT (mean effective dose: 0.22 mSv) were 9.1% (CI [5.2, 15.5]; 11/121) and 20.1% (CI [14.2, 27.7]; 27/134; P = 0.016), respectively. As an additional imaging modality, ULDCT added 9.1% (CI [5.2, 15.5]; 11/121) of main diagnoses to prior CXRs, whereas CXRs did not add a single main diagnosis (0/134; P < 0.001). Notably, ULDCT also offered higher detection rates than CXR for all other clinical relevance categories, including findings clinically irrelevant for the respective emergency department visit with 78.5% (CI [74.0, 82.5]; 278/354) vs. 16.2% (CI [12.7, 20.3]; 58/359) as a primary modality and 68.2% (CI [63.3, 72.8]; 245/359) vs. 2.5% (CI [1.3, 4.7]; 9/354) as an additional imaging modality. Interpretation In non-traumatic emergency department patients, ULDCT of the chest offered more than twice the detection rate for main diagnoses compared to CXR. Funding The Department of Biomedical Imaging and Image-guided Therapy of Medical University of Vienna received funding from 10.13039/501100011699Siemens Healthineers (Erlangen, Germany) to employ two research assistants for one year.


Introduction
Non-traumatic patients accounted for approximately 99 million annual emergency department (ED) visits in the USA in 2017.6][7][8] However, its sensitivity and specificity are moderate, mainly due to superposition of anatomic structures. 9,10In contrast, chest CT offers a three-dimensional (3D) image acquisition without superposition, but with the disadvantages of a markedly higher radiation dose, higher costs, as well as longer examination and reporting times. 11][15][16] In current clinical routine, non-contrast-enhanced chest CTs are performed at two major radiation dose levels, standard-dose CT (SDCT; 6 mSv 3 ) and low-dose CT (LDCT; 1.2 to 2 mSv [16][17][18] ).4][25][26][27][28] However, to the best of the authors' knowledge, there are currently no studies that have evaluated thoracic ULDCT and its intra-patient clinical relevance as a

Research in context
Evidence before this study The PubMed database was searched for studies published in English on ultra-low-dose CT (ULDCT) of the chest published through May of 2023.The search term "('ultra-low-dose' OR 'low-dose') AND ('computed tomography' OR 'CT') AND ('chest' OR 'thorax' OR 'thoracic')" gave 2695 results, while the addition of "AND ('CXR' OR 'chest X-ray' OR 'radiography')" narrowed it to 2129 results, and the further addition of "AND 'emergency'" resulted in 94 studies.The search term "('effective dose' OR 'effective dose conversion coefficient' OR 'radiation dose') AND ('ultra-low-dose' OR 'low-dose') AND ('computed tomography OR 'CT')" yielded 7158 results and the addition of the term "AND 'cancer risk computed tomography'" narrowed this to 1072 studies.We identified 259 studies of interest (published between January 1999 and May 2023).Among these, we identified four studies that assessed ULDCT at a similar dose level compared to CXR, but with different study questions and setups, which we have addressed in detail in the Discussion section.To the best of our knowledge, there are currently no studies evaluating thoracic ULDCT and its intra-patient clinical relevance as a primary imaging alternative to CXR in nontraumatic emergency department patients without limitations on the spectrum of indications constraints on body mass index (BMI).Hence, evidence concerning the clinical relevance of ULDCT of the chest versus CXR in a nontraumatic patient cohort of an emergency department is scarce.

Added value of this study
To the best of our knowledge, this is the first study to conduct an intra-patient comparison of ULDCT of the chest and CXR with regard to their clinical relevance in a nontraumatic patient cohort of an emergency department without limitations on the spectrum of indications or constraints on BMI (n = 294).In this study cohort, ULDCT of the chest offered more than twice the detection rate for main diagnoses compared to chest X-ray.

Implications of all the available evidence
Resources provided, this trial supports the future use of ULDCT as one of the primary chest-imaging modalities in low-prevalence non-traumatic emergency department patients.Due to higher expected costs and resource requirements, further economic analyses will be necessary to determine the optimal spectrum of indications, rationale and economic potential of a broader substitution of ULDCT for CXR as a primary imaging modality of the chest.
primary imaging alternative to CXR in a low-prevalence cohort of non-traumatic ED patients, without limiting the spectrum of indications or BMI.
We hypothesize that the use of thoracic ULDCT as a primary imaging alternative to CXR in a low-prevalence cohort of non-traumatic ED patients, without limitations on the spectrum of indications or constraints on BMI, offers a higher detection rate for all assessed clinical relevance categories.
Therefore, the aim of this trial was to prospectively compare ULDCT and CXR for the detection rate of diagnoses and their clinical relevance in a low-prevalence non-traumatic ED patient cohort.

Trial participants and recruitment
In this trial, non-traumatic emergency department (ED) patients from our institution, with a clinically indicated CXR were included, if written, informed consent was provided.The trial protocol was approved by the local institutional review board (No. 2254/2018) and registered at www.clinicaltrials.gov(NCT03922516), with the acronym UP-Chest trial (ULDCT versus Plain film of the Chest).Patients whose critical condition prohibited two imaging examinations and pregnant women were not eligible for recruitment.Women younger than 55 years were tested for β-HCG.Patient recruitment was carried out daily during the hours of 8.30 am to 2 pm up to a maximum of six patients per day, limited by the available resources at the dedicated CT scanner in the full clinical routine.Within these limits, inclusion was done sequentially.Inclusion and exclusion criteria are summarized in Supplement Table E1.

Trial design
The entry point for all patients of this prospective crossover cohort trial was the clinical indication for a CXR.Trial participants were sequentially examined with both imaging methods, CXR and ULDCT of the chest as an intervention, and then alternately randomized into two arms with an inverse reporting order.For patients in arm A ('arm CXR'), the attending radiology consultant first filed the report on the CXR and only this report was used to determine the detection rate of CXR to avoid an intra-reader bias (Fig. 1).Immediately afterward, the same radiologist read the ULDCT images and filed an additional report based on the imaging data of both examinations to reach the clinically required final intra-reader consensus for that patient.This consensus report was not used for the detection rate of CXR, but only to investigate whether ULDCT could add any information to a prior CXR report.In arm B ('arm ULDCT'), the reporting order was reversed, and the radiology consultant first filed the report on the ULDCT, which was used to assess its detection rate.The subsequent combined report on both imaging examinations was used to determine additional findings of CXR to a prior ULDCT.
All radiological reports were written within the standard clinical workflow at our institution, which included routine access to prior patient history and imaging data.Image reading was performed using the local picture archiving and communication system equipment.Enrolment, allocation to trial arms, and documentation were conducted by the trial coordinator (C.W.).

Compound reference standard and clinical relevance
All prospective imaging reports were transformed into dichotomous radiological report data after the elimination of synonyms, to enable binary comparison for further assessment.
Building of the compound reference standard (CompRS) was a complex, inter-disciplinary, multi-level process, visualized in Fig. 2 and provided in detail in the Supplements.Expert CT radiologists and expert emergency physicians assessed all imaging findings and clinical diagnoses and considered all other available imaging and clinical data up to six months after the end of recruitment to reach a conclusive consensus set of validated imaging findings and diagnoses for every patients initial emergency department visit.Imaging and clinical data after the initial emergency department visit were assessed only to validate or falsify the initial diagnoses in the case of findings and diagnoses that can only be verified over time, such as pulmonary nodules in contrast to acute inflammation.Notably, this CompRS contained radiological findings, as well as clinical diagnoses, including those undetectable by imaging methods.All CompRS elements were stratified with regard to their individual clinical relevance for every patient within the respective hospital visit.The rationale for these clinical relevance categories -similar to Goldman et al. but adapted to the clinical requirements of this trial -is explained in detail in the Supplementary Material. 29The categories ranged from the 'main diagnosis' that caused this ED visit, to 'important incidental diagnosis,' 'strongly contributing,' 'moderately contributing,' and 'clinically irrelevant findings' for this ED visit.Within this trial, the same diagnosis or finding might be classified as a different clinical relevance category in different patients, since in clinical routine the relevance of a finding/diagnosis depends on the patients' individual reason for the specific emergency department visit.Two such examples are given in the Supplementary Material.However, the clinical relevance categories were mutually exclusive within each individual patient.To avoid overemphasis of exclusions of main referring diagnoses, such as 'no signs of pneumothorax,' rule-outs were not classified as a 'main diagnosis,' but only as a 'strongly contributing finding' or 'moderately contributing finding'.However, since the exclusion of frequent thoracic pathologies is one of the main purposes of CXR in emergency medicine, rule-outs of main referring diagnoses were also analysed.

Outcome measures
To assess both imaging methods with regard to clinical relevance, the detection rate for the clinical relevance categories of prospective reports and the proportion of correct results (positive predictive value, PPV) of CXR was calculated from 'arm CXR' (first modality: CXR) and of ULDCT from 'arm ULDCT' (first modality: ULDCT).For both imaging modalities, as a primary and additional imaging modality, the PPV was calculated by comparing the findings of the respective imaging modality against the CompRS.Sensitivity and specificity were not applied, since they are reserved for tests of specific diseases rather than groups of diseases.While the term 'sensitivity' itself it is not applicable to the clinical relevance categories used in our trial, the term 'detection rate' does not As a result of the transformation of imaging reports and the CompRS into dichotomous data, for each patient, our database contains a 0 or a 1 for all 181 different findings observed in this trial.Results were calculated via binary comparison of dichotomous prospective report data against the CompRS for the individual patient.
As is common in clinical routine, a large proportion of ED main diagnoses were not directly visualizable by either ULDCT or CXR (e.g., musculoskeletal thoracic pain or atrial fibrillation).The results, therefore, do not directly reflect the radiological ability of CXR and ULDCT to visualize the respective diseases, but rather their clinical contribution to the final diagnoses.

Changes in patient management
Immediately after reading the report of each imaging examination in this trial, the treating emergency physician was asked to indicate whether the respective examination caused any change in management.Results were acquired separately from each other for the primary and additional imaging modality of both trial arms.

Image acquisition and radiation dose
All CXR examinations were performed with the standard digital chest radiography system at our institution using standard imaging parameters.Depending on mobility and clinical condition, patients were examined in one or two views.ULDCTs were acquired on a thirdgeneration 2 × 128-row Multi-Detector Dual-Source CT System (Somatom Drive, Siemens Healthineers, Erlangen, Germany) using a non-contrast-enhanced CT protocol with 100 kV, tin-filtration, and 50 ref-mAs.Device specifications and imaging protocol details are provided in the Supplements (Tables E2-E3).
3][4] The targeted effective radiation dose of 0.2 mSv for a ULDCT in this trial corresponds to twice the mean effective radiation dose of such a standard CXR examination.Details for the calculation of radiation dose estimates are given in the Supplements.

Statistical analysis
All statistical computations were performed by a biostatistician (M.W.) using IBM SPSS Statistics version 27.0 (© IBM, Armonk, NY).The required number of patients was calculated via power analysis (Supplements).
To compare the two trial arms, unpaired student ttests were used for metric and normally distributed data.In case of skewed metric data, Mann-Whitney-U-tests were used.A chi 2 test was used to compare the sex distribution of the two arms.To compare percentages based on diagnoses (e.g., detections rates or PPV), Generalized Estimation Equations (GEE) were used to consider multiple diagnoses per patient.
Metric data are described using means ± SD.For nominal data, absolute frequencies and percentages are used.A P-value equal to or below 0.05 was considered statistically significant.

Role of the funding source
The Department of Biomedical Imaging and Imageguided Therapy of Medical University of Vienna received funding from Siemens Healthineers (Erlangen, Germany) to employ two research assistants for one year.Limited participation of the funding source in the adaptation of the technical aspects of the applied CT protocols is disclosed.Throughout the trial, all data exclusively remained under the control of the Medical University of Vienna and was never disclosed to third parties.Third parties did not participate in and had no influence on data acquisition, analysis, the conduct, or reporting of this trial.

Patient recruitment and characteristics
Up to six patients per day were recruited from May 2nd to November 26th of 2019.In total, 357 patients were eligible, of which 297 patients were included in this trial.A preliminary analysis revealed a lower drop-out rate than assumed, ensuring the required power for this trial, and therefore, patient inclusion was stopped.Three patients had to be excluded, resulting in a final cohort of 294 patients, 147 in each trial arm (Fig. 1 and Supplements Table E4).Demographic patient characteristics are provided in Table 1 and in the Supplements (Table E5).

Compound reference standard
The Compound Reference Standard (CompRS, all imaging findings and clinical diagnoses) contained a total of 1580 elements, resulting in a mean of 5.4 elements per patient, which showed no significant difference (P = 0.746) between arm CXR (5.3 ± 2.7) and arm ULDCT (5.4 ± 3.0).These 1580 elements contained a total of 314 main diagnoses (including 255 identified main diagnoses and 59 patients for whom no main diagnosis as reason for the respective ED visit was found), 44 important incidental diagnoses, 67 strongly contributing findings, 442 moderately contributing findings, and 713 clinically irrelevant findings.
The most frequent main diagnoses for all patients were 'no  E6).By convention in this trial, only such direct confirmations of the CompRS by imaging were considered true-positives.The main diagnosis 'no main diagnosis found' was, therefore, excluded from the detection rate calculation.

Reporting performance of CXR and ULDCT
As a first imaging modality, prospective ULDCT reports (Arm B) contained a significantly higher number of findings and diagnoses than CXR with a total of 574 vs. 257 (P < 0.001).Of these, 546 (ULDCT) and 192 (CXR) were verified in the CompRS (P < 0.001), resulting in a significantly higher positive predictive value of 95  3, Fig. 3, Fig. 4 and in the Supplements (Table E6).Examples are provided in Fig. 5, Fig. 6 and in the Supplements (Figures E1-E3).
The observed advantages of ULDCT are more pronounced when it is used as an additional imaging modality after CXR.ULDCT added significantly more findings and diagnoses (n = 365) to prior CXR reports than vice versa (n = 32, P < 0.001), of which 354 ULDCT and 17 CXR findings and diagnoses were verified in the CompRS resulting in a significantly higher PPV for ULDCT of 97.0%CI [94. 7, 98.3]   To avoid an intra-reader bias, the determination of the detection rate was derived exclusively from the first imaging modality of the respective case.Notably, findings and diagnoses were stratified with regard to their individual clinical relevance for every patient within the respective hospital visit.a Clinically irrelevant for the respective hospital visit at the emergency department.low for both modalities and the difference was not statistically significant (P = 0.053), the results indicate a higher reliability for correct exclusions by ULDCT.The clinical relevance of the correct exclusions was rated as a strongly contributing finding in 24 (22.0%) and as a moderately contributing finding in 84 (77.1%) patients.Only one (0.9%) exclusion was considered clinically irrelevant.Detailed results are shown in Table 2.

Radiation dose
The measured mean dose area product (DAP) for CXRs of the average patient in this trial was 3.7 dGy*cm 2 (±2.9), corresponding to a mean effective radiation dose of 0.05 mSv (±0.04).The mean radiation dose of a CXR in this trial was, therefore, approximately half the mean radiation dose of a standard CXR examination in the USA.Depending on mobility and clinical condition, patients were examined in one (n = 19)  Notably, findings and diagnoses were stratified with regard to their individual clinical relevance for every patient within the respective hospital visit.a Clinically irrelevant for the respective hospital visit at the emergency department.
Table 4: Detection rate of CXR and ULDCT as additional imaging modality (CXR after ULDCT in 'Arm ULDCT' and ULDCT after CXR in 'Arm CXR').(n = 275).The mean total dose length product (DLP) for the ULDCT scans, including the scan projection radiograph (scout view), was 12.7 mGy*cm (±4.2).This corresponds to a mean effective dose of 0.22 mSv (±0.07), and therefore, approximately 4.5 times the mean effective dose of a clinical CXR at our institution or twice the radiation dose of a standard CXR in two views (mean dose levels).Detailed information is provided in the Supplements (Table E7, Figure E1).

In-room time and reporting time
ULDCT required a longer mean in-room time (5.1 vs. 2.1 min) and mean reporting time (4.8 vs. 1.8 min) than CXR (Supplements Table E8).

Discussion
In this prospective crossover trial of a low-prevalence non-traumatic emergency department patient cohort, we found that, on an intra-patient level, the detection rate for clinically relevant findings and diagnoses of ultra-low-dose CT (ULDCT) of the chest is superior to chest X-ray (CXR) at a radiation dose equal to approximately 4.5 clinical CXRs at our institution.As a primary imaging modality, ULDCT offered about twice the detection rate of CXR for main diagnoses and moderately contributing findings.Furthermore, ULDCT significantly increased the overall detection rate for main diagnoses when used as an additional modality after CXR, while CXR after ULDCT was unable to detect any further main diagnoses.This superiority is also reflected in the moderately contributing findings, important incidental diagnoses, rule outs and triggered management changes, for the use as primary as well as additional imaging modality.Notably, ULDCT detected more than twice as many findings classified as clinically irrelevant for the respective hospital visit than did CXR, which might be considered a disadvantage of this imaging method.However, it is important to point out that these findings might still be relevant for further diagnostic workup and non-acute therapy of these patients (e.g., coronary atherosclerosis, calcifications of cardiac valves, pulmonary emphysema).
For our trial cohort, the most frequent 'main diagnosis' detected by both imaging methods was 'pneumonia.' Beyond a significantly higher detection rate for pneumonia itself, ULDCT contributed several additional intrapulmonary (e.g., bronchiolitis and intrapulmonary masses) as well as extrapulmonary 'main diagnoses,' while almost all 'main diagnoses' directly found by CXR were limited to pneumonia, confirming the limited value of CXR in non-traumatic ED patients.
The assessment of the efficacy of diagnostic imaging has a long history in the radiologic community.In 1991, Fryback, Thornbury et al. published a hierarchical model as an organising structure for the appraisal of efficacy studies in diagnostic medical imaging. 37This scale categorises efficacy studies of imaging tests into the following six levels: Level 1 "technical efficacy," level 2 "diagnostic accuracy efficacy," level 3 "diagnostic thinking efficacy," level 4 "therapeutic efficacy," level 5 "patient outcome efficacy," and level 6 "societal efficacy."We emphasise that these levels should be used for categorisation of the respective study to provide comparability to existing literature and do not reflect the value of a study.Therefore, we provide the level of efficacy according to the Fryback-Thornbury efficacy scale for each study cited in this discussion.
Kroft et al. 38 conducted a study (partially including Fryback-Thornbury Level 2, 3 and 4) with 200 patients referred by outpatient clinics or general practitioners, and, per study design, assessed the added value of ULDCT (mean effective dose [mED]: 0.07 mSv) after CXR.They found that the diagnostic confidence of the radiologist increased from 88% for the CXR to 98% after the additional ULDCT.Furthermore, the authors reported management changes caused by the additional information of ULDCT in 40 patients (20%).In contrast, our trial assessed the primary detection rate of both modalities, their additional value if used as second imaging modality, an analysis of exclusions of main referring diagnoses, and the clinical relevance and contribution of CXR and ULDCT to the final clinical diagnoses, while taking into account that not all of them are radiologically visualizable.
One of the most recent studies comparing ULDCT (mED: 0.05 mSv) and CXR was published by Taekker et al. 30 in 2021 (Fryback-Thornbury Level 2).It prospectively included 91 emergency department patients with a clinical indication for a CXR in supine view (sCXR), who received a ULDCT and non-contrast SDCT of the chest in addition to the indicated sCXR.The authors retrospectively assessed four predefined chest conditions, whereas in our trial all patients with an indication for a CXR were eligible.Taekker et al. reported superior sensitivity for ULDCT compared to sCXR in the detection of pneumonia (90-100% vs. 50-80%) and pneumothorax (25-50% vs. 0%), while sensitivity was similar for pulmonary edema (0-56% vs. 0-78%) and pleural effusion (48-72% vs. 59-66%).
In contrast to these studies, a recent multicentre trial with 2418 non-traumatic ED patients by van den Berk et al. 39 (OPTIMACT study group; Fryback-Thornbury Level 4 and 5) was designed as a noninferiority trial with the focus on short-term patient outcomes after examination by either ULDCT or CXR.The authors found no inferiority of ULDCT, and only minimal differences in length of ED stay, hospital admissions, length of hospital stay, functional health at 28 days, as well as mortality rates between the two imaging modalities.Due to the wider availability and lower costs, they recommended the continued use of CXR as a primary modality in such an ED patient cohort.While both trials, van den Berk et al. and ours, assessed ULDCT and CXR in non-traumatic ED patients, they starkly differ regarding the trial design, including the outcome measures and time points of their assessment.In our trial, detection rates of clinical diagnoses, the clinical relevance, and exclusion performance were measured at the beginning of the diagnostic workflow, while van den Berk et al. 39 measured the length of the hospital stay, functional health at 28 days, and mortality.The design of the latter trial, where patients would receive either CXR or ULDCT, prevented an intra-patient comparison of the modalities and may have resulted in a lower certainty for diagnoses.Furthermore, as described by the authors, the advantages of CXR with regard to time and costs may be limited by the significantly higher number of patients who required additional imaging examinations after CXR than after ULDCT.Therefore, the results cannot be directly compared.However, both trials shine light on the primary imaging modalities for non-traumatic ED patients from different angles and may contribute to further evidence-based discussion on this topic.
In contrast to the discussed literature, in our trial, assessed diagnoses were not limited to radiologically visible diagnoses, each finding and diagnosis was assigned to an individual clinical relevance category, and patients were eligible for participation regardless of indication for CXR, pre-existing conditions, or BMI.On the hierarchical Fryback-Thornbury scale 37 we would categorise this trial as Level 3 and 4. Further strengths of our trial are that all patients were examined with both imaging modalities, 39 CXRs were not limited to supine view or to the assessment of specific groups of diagnoses or findings. 30egarding radiation protection, it is important to emphasize that this trial analysed ULDCT (only twice the radiation dose of a standard CXR) as an imaging alternative to CXR in non-traumatic emergency department patients, and both modalities assessed in this trial are at the lowest bound of radiation exposure in diagnostic medical imaging.At this level, radiation risks are so low that they are not measurable by epidemiological studies. 40,41By way of illustration, the mean radiation dose of 0.22 mSv for a ULDCT in this trial, 0.1 mSv for a standard CXR examination, and 0.05 mSv for a CXR in this trial, correspond to 26, 12, and six days of natural background radiation, respectively. 3,42his trial has several limitations.While an intrareader bias was eliminated by using only the first imaging modality of the respective arm for the determination of the detection rate of CXR and ULDCT, the assignment of the clinical relevance categories might be prone to a confirmation bias.In order to reduce this potential bias, final clinical diagnoses were determined by experienced emergency physicians.Also, this trial focused on the clinical relevance of diagnoses and findings by imaging, and therefore, objective and subjective image quality were not evaluated.In addition, patient inclusion regardless of indication resulted in a large variety of diseases, a limited number of patients per disease, and a substantial proportion of patients without abnormal findings.Furthermore, this was a single-centre trial, but in-room time and reporting time are expected to vary among institutions due to different organizational frameworks and workflows in radiology departments.Since the main inclusion criteria was an indication for CXR only, the trial protocol did not include a standard-dose CT, which might have revealed additional findings.However, a comparison of ULDCT to SDCT was beyond the scope of this trial.Finally, the observed higher number of clinically irrelevant findings in reports of ULDCT compared to CXR may lead to unnecessary follow-up examinations.
4][45] Further studies are necessary to determine the rationale and economic aspects of such a substitution and, especially, to determine whether the observed benefits would justify the additional efforts.
In conclusion, ULDCT of the chest proved to be superior to CXR in a low-prevalence non-traumatic ED outpatient patient cohort.While ULDCT required a radiation dose of approximately 4.5 clinical CXRs at our institution or only two standard CXR examinations, the observed advantages with regard to the detection rate for ULDCT, including the doubling in the percentage of directly detected main diagnoses, support its use as one of the primary imaging modalities in the ED in the future.Further economic analyses will be necessary to determine the optimal spectrum of indications, rationale, and economic potential of a broader substitution of tion, Resources, Software, Supervision, Validation, Visualization, Writingoriginal draft, Writingreview & editing.
Christian Wassipaul and Helmut Ringl have accessed and verified all data.

Data sharing statement
The anonymized participant data on which this study is based will be made available upon request by email to the corresponding author by qualified researchers after publication.No imaging data exceeding the images provided in this manuscript can be made available.Proposals will be approved by the authors on the basis of scientific merit and absence of competing interests after the signing of a data access agreement and confidentiality agreement.

Declaration of interests
The Department of Biomedical Imaging and Image-guided Therapy of Medical University of Vienna has grants and contracts with more than 100 partners (organizational, academic, industry), all through official contracts with the Medical University of Vienna.Among these was funding from Siemens Healthineers (Erlangen, Germany) to employ two research assistants for one year for this study as well as grants independent of this study.CW was employed as research assistant by Medical University of Vienna for one year, enabled by funding from Siemens Healthineers and furthermore reports support for congress fees, travel and accommodation costs, unrelated to this study, by Medical University of Vienna.DT reports consulting fees from Roche and Siemens Healthineers, support for attending meetings and/or travel from Siemens Healthineers and participation on the DSM board, all unrelated to this study.HP reports honoraria as a speaker from Astra-Zeneca, BMS, Boehringer Ingelheim, Janssen, MSD, Novartis, Roche, Sanofi, Siemens Healthcare and Takeda as well as participation on the advisory board of AstraZeneca, Boehringer Ingelheim, Janssen, MSD and Sanofi, all unrelated to this study.MS reports support for congress fees, travel and accommodation costs, unrelated to this study, by Medical University of Vienna.RES reports honoraria as an educational speaker from Siemens Healthineers and a pending patent developed with Siemens Healthineers, all unrelated to this study.PA reports honoraria as a speaker from Siemens Healthineers, unrelated to this study.WB reports unpaid participation on the editorial board of Medical Physics and Zeitschrift fuer Medizinische Physik, both unrelated to this study.CH reports unpaid participation on the Photon Counting CT advisory board of Siemens Healthineers as well as stock ownership of Hologic until 2021, all unrelated to this study.HR was the PI of grants to the Medical University of Vienna from Siemens Healthineers until June 2018 and is still scientifically involved in several studies concerning these grants, but did not and does not receive remuneration nor is he part of the contracts; HR further reports honoraria as a clinical speaker from Siemens Healthineers until December 2019 and unpaid participation on the editorial board of European Radiology.The other authors declare no further competing interests.

Fig. 1 :
Fig. 1: Prospective trial workflow within the clinical routine.Using only the first imaging modality of the respective arm for the determination of detection rate of CXR and ULDCT, this setup was chosen to exclude an intra-reader bias.

Fig. 4 :
Fig.4: Additional findings and diagnoses by CXR and ULDCT.Proportion of 'main diagnoses,' 'important incidental diagnoses,' 'strong contributing findings,' 'moderately contributing findings,' and 'clinically irrelevant findings' added by CXR to prior ULDCT (in arm B) and by ULDCT to prior CXR (in arm A) relative to the total number in the Compound Reference Standard of the respective arm.

Fig. 5 :
Fig. 5: Example A. A 38-year-old male patient who presented with dyspnoea, cough, and fever of up to 39 • C for two weeks and no improvement under antibiotics.CXR showed moderate bronchial wall thickening (A), but ULDCT detected extensive bilateral centrilobular nodules (B, C-white arrowheads) with basal predominance, consistent with bronchiolitis.

Fig. 6 :
Fig. 6: Example B. A 52-year-old female patient with a history of smoking, COPD, and prior oral cancer who presented with an impaired general condition and elevated CRP.The CXR report described only findings consistent with pulmonary emphysema.The following ULDCT additionally detected a pulmonary nodule suspicious for malignancy of the central left apical lower lobe (C, D-white arrows).Retrospectively, with the knowledge of the ULDCT, this nodule could be also suspected on CXR in superposition of the left pulmonary artery (A, B -white arrowheads).

Table 1 :
Patient demographics and symptoms at presentation.
Notably, the Compound Reference Standard contained radiological findings, as well as clinical diagnoses, including those undetectable by imaging methods.We emphasise, that "no main diagnosis found" (n = 59) is not included in this table.

Table 2 :
Diagnoses and findings directly detected by CXR and ULDCT in relation to the Compound Reference Standard.

Table 3 :
Detection rate of CXR and ULDCT as primary imaging modality (CXR in 'Arm CXR' and ULDCT in 'Arm ULDCT').
or two viewsArm ULDCT: Additional findings and diagnoses added by CXR to prior ULDCT reports